The compound 2-(2'-thienyl)ethylamine is a known compound useful in the synthesis of a pharmaceutical drug known generically as ticlopidine hydrochloride. The compound 2-(2'-thienyl)ethylamine has the following structural formula (I): ##STR3## The compound of formula (I) as well as other related alkylamines of formula I(a) are not stable when subjected to an oxygen containing atmosphere. ##STR4## The air instability problem with 2-(2'-thienyl)ethylamine is a serious problem in that: (1) the compound (I) is not inexpensive to produce and loss of compound (I) to oxidation increases costs; and (2) a high degree of purity is needed in the manufacture of pharmaceutical compounds. The present invention virtually eliminates the instability problem by converting the compound of formula (I) to the carbamate salt of structural formula (II). ##STR5##
The significance of the present invention can be realized in part by referring to earlier patents disclosing ticlopidine, related compounds and their methods of synthesis.
U.S Pat. No. 4,051,141, issued Sept. 27, 1977, discloses thieno[3,2-c]pyridine derivative compounds having the formula (III): ##STR6## wherein R is a phenyl or benzoyl radical optionally substituted with 1-3 halogen atoms or lower alkyl, lower alkoxy, hydroxy or nitro; R.sub.1 is hydrogen, halogen, hydroxy or lower alkyl; R.sub.2 is hydrogen or halogen and n is 1 or 2, and in which the symbols R.sub.1 may be different in each CHR.sub.1 when n is 2; and their pharmaceutically acceptable acid addition salts.
Of these compounds, perhaps the most interesting is when R.sub.1 and R.sub.2 are H, n is 1 and R is o-chlorobenzyl. Such a compound is known chemically as 5-[(2-chlorophenyl) methyl]-4,5,6,7-tetrahydrothieno-[3,2-c]pyridine hydrochloride, more commonly known as ticlopidine and most commonly referred to as the hydrochloride salt thereof. Ticlopidine is a known and useful pharmaceutical compound.
In that the present invention includes a method for making and purifying an intermediate useful in the synthesis of ticlopidine, U.S. Pat. No. 4,051,141 is incorporated herein by reference for purposes of disclosing ticlopidine, its intermediates and related compounds as well as methods making, using and/or administering ticlopidine, its various salts, esters and related compounds. In addition, U.S. Pat. No. 4,127,580, issued Nov. 28, 1978, is incorporated herein by reference for its disclosure of ticlopidine, its intermediates and related compounds as well as methods for making such compounds. The present invention was specifically developed to aid in the synthesis of ticlopidine by improving the air stability of the intermediate of formula (I).
The compound (I) and its method of synthesis are needed to carry out the present invention. Although compound (I) is known, so that this disclosure will be self contained the following disclosure is provided regarding compound (I).